Method of treating the oral cavity with oral hygiene preparations containing active SnF2

ABSTRACT

This invention relates to a method of treating the oral cavity with ingestible, non-foaming, non aqueous, liquid and semi-solid oral hygiene preparations containing: a nonionic surfactant, a coating substance insoluble in said surfactant and a microbially active form of stannous fluoride.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation-in-part of copending application Ser.Nos.: 06/927,752, filed Nov. 6, 1986 and 06/927,805, filed Nov. 6, 1986,now U.S. Pat. No. 4,950,479, the disclosures of which are herebyincorporated herein by reference.

FIELD OF THE INVENTION

This invention relates to a method of treating the oral cavity withingestible, non-foaming, nonaqueous liquid and semi-solid, oral hygienepreparations containing a nonionic surfactant, a coating substanceinsoluble in said surfactant, and a microbially active form of stannousfluoride (SnF₂) These oral hygiene preparations have utility in treatingcaries, plaque fighting and in gingivitis control as well as for thetreatment of hypersensitive teeth, various Candida so. conditions, andother disorders of the oral cavity. These oral hygiene preparations canbe delivered to the oral cavity in several forms including: sprays,pre-rinses, rinses, pastes, gels and creams. Generally the oral hygienepreparations of the present invention are stored and used in dispensersthat do not take on oxygen and/or water over the life of the product.

BACKGROUND OF THE INVENTION

Stannous fluoride, SnF₂, has been used in dentistry since the 1950's asa chemical adjunct to prevent dental caries. Topical applications ofSnF₂ consistently have shown dramatic reductions in dental cariesactivity with minimal side effect. Evidence has also accumulated thatSnF₂ has antibacterial properties which may affect its anticariesproperties as well as inhibit plaque formation and gingivitis. SeeTinanoff, "Review of the Antimicrobial Action of Stannous Fluoride,"1990.

Addy et al., 1988, reported a densensitizing effect for fresh SnF₂ dueto a covering or obturation of tubules in hypersensitive dentine. Thereis also an indication that SnF₂ may be effective in controlling Candidasp. colorization of denture plaque.

Prescription (R_(x)) nonaqueous gels of glycerine and SnF₂, such asScherer Laboratory's, Gel-Kem are perhaps the most widely used form ofR_(x) SnF₂ available commercially. These gels are generally prescribedfor the treatment of caries, hypersensitive teeth as well as gingivitis.

Unfortunately, in spite of its promising results, the effective use ofSnF₂ has been drastically limited by its inherent instability in thepresence of oxygen, water, abrasives etc.

In addition to the inherent instability of SnF₂, most SnF₂ productssuffer from poor patient compliance, attributed in part to thenonaqueous carriers required to maintain activity, to the metallic tasteof the product, as well as to the methods of application, which usuallyinclude a brushing step separate and apart from the use of a dentifrice.For example, brush-on SnF₂ gels require the patient to brush at leastfour times/day, i.e., twice with the gel and twice with a regulardentifrice. Compliance in such a treatment regimen drops about 30%, anunacceptable level, as documented by Hastrieter's review of Wolf etal.'s 1989 Gel-Kem study.

With the advent of fluoride in water and fluoridated dentifrices, gumdisease, gingivitis, hypersensitive teeth, root caries in the elderlyand candida disorders in denture wearers, have replaced caries inchildren as the dominant oral care concerns of the '90's requiringspecial treatment. For example, a recent NIH survey established 90% ofadults 65 or older have some form of gum disease, and over 123 millionadults in the U.S. suffer from gum disease. Moreover, one out of sixadults suffer from hypersensitivity at one time or another, while tenmillion adults are chronic sufferers. Additionally, the millions ofadults who undergo periodontal treatment, or have their teeth cleaned,experience hypersensitivity discomfort ranging from an uncomfortablefeeling to severe pain. Most denture wearers suffer from "denturebreath" attributed in part to Candida sp. colonization of denture plaqueand/or plaque-like coatings on dentures.

Recent reviews on dentine hypersensitivity have deduced that thetransmission of pain stimuli across dentine is by a hydrodynamicmechanism. This is confirmed by the open tubules (microscopic openings)present at the dentine surface of sensitive teeth (and not present innormal teeth). Various stimuli cause fluid movement in these tubuleswhich activate nerve endings in the pulp.

Considerable evidence has accumulated in the past 20 years to show thattopical applications of SnF₂ reduce S. mutans levels as well asdemonstrate antiplaque properties. These antiplaque and antigingivitisbenefits of SnF₂ appear to be related to frequent, i.e., severaltimes/day treatment with SnF₂.

Root caries in the elderly is attributed to the recession of gums and isa common condition in the elderly that fortunately does respond tofluoride treatment. Candida sp. yeast disorders are estimated to occurin approximately 90% of denture wearers. These disorders lead to, or areassociated with, stomatitis and thrush (candidiasis).

There is therefore a definite need in the art for oral hygienepreparations containing microbially active SnF₂ that retain the desiredantibacterial activity over the use life of the preparations. There isalso a need in the art for oral hygiene preparations containingmicrobially active SnF₂ that are pleasant to use, encourage complianceand support frequent usage throughout the day. There is a further needin the art for new methods of treating caries, coronal caries,gingivitis, plaque buildup, hypersensitivity and Candida sp. infectionsof denture plaque with microbially active SnF₂ products in variousforms.

There is a further need in the art for delivery vehicles for microbiallyactive SnF₂ which achieve rapid transport of SnF₂ into fissures,crevices in dentures and other prosthesis where the microbial activityof SnF₂ can be employed to fight plaque and disrupt the colonization ofdenture plaque by yeast type organisms while protecting the SnF₂ fromdegradation of its microbial activity.

In view of the foregoing it is an object of this invention to provide anoral hygiene preparation containing a microbially active form of SnF₂for treating caries, gingivitis, plaque buildup hypersensitivity andCandida sp. infections of denture plaque.

It is also an object of this invention to provide an oral hygienepreparation containing microbially active SnF₂ that is pleasant to use,encourages compliance and repetitive usage.

It is a further object of this invention to provide an effective methodfor treating caries, gingivitis, hypersensitivity, plaque buildup andCandida sp. infections of denture plaque.

It is still a further object of this invention to provide a compatiblevehicle for microbially active SnF₂ that permeates crevices etc. indentures and denture plaque to deliver the active SnF₂ so it can fightdenture plaque and control colonization of denture plaque by Candida sp.organisms.

It is yet another object of this invention to provide a method ofmanufacturing oral hygiene preparations containing a microbially activeform of SnF₂.

SUMMARY OF THE INVENTION

In accordance with the foregoing objectives, this invention providesoral hygiene preparations containing microbially active forms ofstannous fluoride (SnF₂) that are useful for treating caries,gingivitis, Candida sp. infections of denture plaque, hypersensitivityand plaque buildup. The preparations of the present invention areingestible, non-foaming, nonaqueous, abrasive free, liquids andsemi-solids that contain a nonionic surfactant, a coating substanceinsoluble in said surfactant and a microbially active form of SnF₂.

The preparations of the present invention can be introduced into theoral cavity in several forms including: sprays, pre-rinses, gels, pastesand creams. Generally, the preparations of the present invention arestored and used in dispensers that are free from oxidation, hydrolysis,and free from any substances that interfere with the microbial activityof SnF₂.

The preparations of the present invention are substantive to the hardand soft tissue in the oral cavity and have a pH from between about 3.4and about 6.5.

DETAILED DESCRIPTION OF THE INVENTION

As described above, the oral hygiene preparations of this invention areingestible, non-foaming, nonaqueous, abrasive free, liquids andsemi-solids that contain a nonionic surfactant, a coating substanceinsoluble in said surfactant and a microbially active form of SnF₂.These preparations are substantive to the hard and soft tissue in theoral cavity.

The term nonaqueous, as used in the present invention, is defined asbeing essentially free from active water. That is, there is no "active"water available in the preparation to hydrolyze the microbially activeSnF₂. While some minute amount of water may be present is generally acertainty, under most conditions (e.g., from relative humidity) but suchwater is not deemed "active" herein.

The term microbially active stannous fluoride, as used in the presentinvention, is defined as stannous fluoride that exhibits antimicrobialactivity towards S. mutans when assayed according to either Camosci andTinanoff, Journal Dental Research, 1984, 63: 1121 et. seq., or Ota etal., Pediatric Dentistry, March 1989, Vol. II, Number P.21-25.

"Fresh" stannous fluoride exhibits the antimicrobial properties suitablefor the purposes of the present invention. However, to avoid anycontroversy surrounding the use of the term "fresh", i.e., "how-fresh"etc., for the purposes of the present invention this form of stannousfluoride can also be described as being in its "native" solvated staterather than "fresh." Reliance upon chemical assay for Sn⁺⁺ species isnot an adequate measurement of Sn⁺⁺ microbial activity, as many stannousion species are microbially inactive.

The term non-foaming, for the purposes of the present invention, isdefined as producing little or no foam during application of thepreparation of the invention to the oral cavity, so as to cause nodiscomfort or gagging.

The term ingestible, as used in the present invention, is defined ascapable of being ingested with no risk of danger to the subject beingtreated.

Free from abrasives, for the purposes of the present invention, isdefined as containing no abrasive, nor abrasive-like substance normallyused in dentifrices, or containing trace amounts of these substancessuch that their characteristics abrasive action cannot be perceived northeir adverse effect on microbially active SnF₂ established.

Rinse and pre-rinse, for the purposes of the present invention, includethose concentrates of rinses and pre-rinses that are to be mixed withwater prior to introducing into the oral cavity. Generally theseconcentrations are dispensed into a cup with 10 to 15 ml of tap waterfrom hermetically sealed package.

The nonionic surfactants, suitable for the present invention includeblock copolymer mixtures of polyoxyalkylene compounds, i.e., poloxamersincluding ethylene oxide and propylene oxide poloxamer mixtures; such asthose described in U.S. Pat. Nos. 4,343,7B5: 4,465,663; 4,511,563; and4,476,107, the disclosures of which are hereby incorporated herein byreference. Commercial versions of these nonionic poloxamer surfactantsare available from BASF--Wyandotte Co., Wyandotte, MI and includevarious Pluronics such as Pluronic F108 and F127 and those Pluronicsdescribed in "Pluronic & Tetronic Surfactants", BASF Corp., 1987, atpage 2. Other suitable nonionic surfactants useful in the gels of thepresent invention include: polyoxyethylene sorbitan monoleate(Polysorbate 80); polyethylene glycols (Pluracols); nonylphenolethoxylates (Surfonics); linear alcohol ethoxylates polyethyleneglycolparaisooctypheny/ethers (Tritons's) and those described in Tables I andII below.

The nonionic surfactants in the preparations of the present inventionare preferably employed at levels ranging from about 0.1% to about 50%by weight of the composition, and most preferably from about 0.5% toabout 10% by weight of the liquid preparations of the invention and upto 30% in the semi-solids. In general, the amount of nonionic surfactantemployed can be adjusted to provide the desired degree of cleaning,conditioning, physical form and treatment desired.

In the present invention, a coating substance is employed in combinationwith the nonionic surfactant component of the preparation. The coatingsubstances suitable for the preparations of the invention are insolublein the surfactant and can be characterized as follows, they:

1. suppress the tendency of the surfactant to foam,

2. are safely ingestible at the concentrations used,

3. have an affinity for hard and soft surfaces in the oral cavities,

4. are neural, inert and do not support microbiological activity,

5. modify the surface energy properties of gums and teeth such that itis more difficult for food particles, cellular debris and various plaqueprecursors and formers to attach to these surfaces,

6. form a thin, transparent coating that does not build up on the gumsand teeth and is removed by the normal clearing and flushing action ofthe mouth,

7. impart a pleasant "smooth" feeling to the surfaces of the oralcavity, and

8. retain various flavors and substances on surfaces of the oral cavityimparting an unexpected prolonged flavor effect and do not interferewith the microbial activity of SnF₂.

Suitable coating substances for the preparations of the presentinvention include various silicones insoluble in the nonionicsurfactants used in the present invention including polyalkylsiloxanessuch as polydimethysiloxanes, such as Dow Corning 360 Medical Fluid atviscosities of 20 to 12,5000 centistokes; Dow Corning Q7-2587Simethicone Emulsion; Dow Corning 200 Fluids, 60,000 to 100,000centistokes with the chemical composition CH₃ SiO[SiO(CH₃)₃ ; allavailable from Dow Corning, Midland, MI.

The coating substances of the preparations of the present invention arepreferably employed at levels ranging from about 0.01 to about 0.5% byweight of the composition; and most preferably from between about 0.05and about 0.25% by weight of the preparations. For semi-solidpreparations of the invention the coating substances are present at frombetween about 0.05% and about 4% by weight. In general, the amount ofcoating substance employed is adjusted to provide the desired degree ofconditioning and substantivity for the treatment desired.

The weight ratio of nonionic surfactant to coating substance in thepreparations of the present invention range from between about 100:1 toabout 2:1 and preferably from between about 17:1 to about 3:1.

Stannous fluoride (SnF₂) U.S.P. powder, available from Ozark Mahoning,Tulsa, OK, is suitable for the preparations of the present invention.Generally, the stannous fluoride when used in the various preparationsof the present invention which are applied directly into the oral cavityis at concentrations from between about 0.05% and about 0.4% by weight.

For those preparations of the present invention which are to be used asdilutable concentrates, such as the pre-rinse and rinse concentratesdescribed below, or as sprays for the treatment of prosthesis;concentrations of SnF₂ ranging from between about 0.4% to about 10% byweight can be used. Normally, the upper limit of SnF₂ concentration isdetermined by the solubility of SnF₂ in the formulation chosen andsafety in use considerations.

The combination of certain nonionic surfactants with certain coatingsubstances and microbially active stannous fluoride in the preparationsof the invention, wherein the coating substance is insoluble in thesurfactant is novel. The anticaries, antiplaque, gingivitis controlrelief of hypersensitivity and anti-Candida sp. results obtained withthe preparations of the present invention are attributed in part to:

a. the microbial activity of stannous fluoride obtained with thesepreparations,

b. the excellent compliance profile the preparations of the presentinvention exhibit during clinical evaluations,

c. the mouth feel and improved hedonics that characterize thesepreparations,

d. the modes of delivery used to introduce these preparations into theoral cavity, and

e. the cleaning, conditioning and treating of hard and soft tissue inthe oral cavity that results from the use of the preparations of theinvention.

In one embodiment of the present invention, the preparations of thepresent invention, in liquid form, are delivered to the oral cavity assprays which include various extenders such as propylene glycol,glycerin, sorbitol/hydrogenated glucose syrup mixtures, and ethanol.These liquid sprays are free from active water and are preferablydispensed into the oral cavity from a hermetically sealed package suchas an aerosol spray device. An example of a liquid spray is described indetail in Example 1 below. Illustrative examples of sprays and otherliquids of the invention are further described in Table I.

These sprays are particularly useful in reducing plaque and controllinggingivitis, when they are introduced into the oral cavity several timesper day, thereby capitalizing on the substantivity of the microbiallyactive stannous fluoride. When used four to five times per day thesesprays have the potential to maintain microbially active stannousfluoride in the oral cavity at levels sufficient to control plaquebuildup, reduce bleeding sites and gingivitis and treat Candida sp.infections.

The sprays of the present invention can also be used to treathypersensitive teeth and root caries in the elderly as well as caries inyoungsters. The sprays described herein have the highest compliancepotential of all the delivery forms of the preparations of the presentinvention, not only because of their advanced hedonics but also due totheir convenient form of delivery, i.e., the sprays can be carried inpocket or purse and can be used anywhere throughout the day.

The sprays can also be applied to prosthesis to clean, condition andtreat the prosthesis for Candida sp. contamination which leads tostomatitis and thrush. See Table I.

In a second embodiment of the invention the preparations of the presentinvention, in a liquid form, are delivered to the oral cavity as rinsesor pre-rinses which include various extenders, etc. such as described indetail in the examples below. These concentrated rinses and pre-rinsesare preferably dispensed from a hermetically sealed dispenser or acollapsible tube into a container and diluted with water prior to use.Illustrative Examples of the rinse, pre-rinse concentrates of thepresent invention are described in Table II below.

The rinse and pre-rinse concentrates of the present invention areparticularly useful in fighting plaque, reducing plaque buildup andcontrolling gingivitis. The rinses and pre-rinse concentrate modes ofdelivery can also be used as anticaries and hypersensitivity treatmentsand in this regard are particularly useful for treating root caries andhypersensitive teeth in the elderly.

In another embodiment of the invention, the preparations of the presentinvention, in a semi-solid form such as a paste, are delivered to theoral cavity from various sealed dispensers including collapsible tubes.Preferably, these pastes are brushed onto the surfaces of the teeth andgums or rubbed into these surfaces with a finger or a swab or a gauze.Illustrative examples of the pastes of the present invention aredescribed below.

The pastes of the present invention are particularly useful in treatingroot caries and hypersensitive teeth in adults. These pastes aregenerally applied to the areas to be treated by dispensing the pasteonto a finger and rubbing the finger over the area to be treated. Whenthe pastes are dispensed from collapsible tubes ranging from about 1/3oz. to about 1 oz. in size, they can be carried in pocket or purse andeasily applied several items a day outside the bathroom. Generally, thepatient also brushes their teeth twice a day with a traditionaldentifrice applying the paste after each brushing. Regular use of atraditional dentifrice generally controls the staining that can occurwith certain patients who use microbially active stannous fluoride.

In still another embodiment of the invention the preparations of thepresent invention, in a gel form, are delivered to the oral cavity fromvarious sealed dispensers, including collapsible tubes. Preferably thesegels are brushed onto the surfaces of the teeth and gums or rubbed ontothese surfaces with a finger or gauze or a swab. Illustrative examplesof the gels of the present invention are described in Table II below.

The gels of the present invention are particularly useful in treatinggum disease, gingivitis and plaque buildup. They can be dispensed fromconvenient size tubes that can be carried in pocket or purse and appliedthroughout the day to the area to be treated. Generally, they areapplied after brushing with a traditional dentifrice. It is notnecessary to rinse the gels from the mouth since they are pleasanttasting. These gels are perceived to be present and working often times30 minutes after they have been applied to the area to be treated.

In yet another embodiment of the invention the preparations of thepresent invention, in a cream form, are delivered to the oral cavityfrom various sealed dispensers including collapsible tubes. Preferably,these creams are brushed or rubbed onto the surfaces to be treated usinga soft bristled brush, a finger or a swab. Illustrative examples ofthese creams are described in Table III below.

The creams of the present invention are particularly useful in treatinggum disease, gingivitis and plaque buildup. They can be dispensed fromconvenient size tubes that can be carried in pocket or purse and appliedthroughout the day to the areas to be treated. Generally they areapplied after brushing with a dentifrice. It is not necessary to rinseafter applying these creams, since they are most pleasant tasting andleave a fresh clean feeling in the mouth.

The cleaning of plaque-like films from the teeth and gums with thepreparations of the present invention is achieved with a minimum ofmechanical action and without foaming. After the cleaning and treatingstep there is no need to expectorate nor to rinse the preparation of thepresent invention from the mouth. The coating that remains on thesurfaces of the oral cavity leaves these surfaces feeling smooth andclean. This coating contains an appropriate flavorant, such that thecontinuing treatment is a pleasant experience which encouragescompliance, i.e., regular usage.

The films remaining on the surfaces of the oral cavity are notmetabolizable by resident oral cavity microorganisms and are substantiveto various surfaces of the oral cavity, unlike natural film formers suchas lecithin which are also substantive to soft tissue, but which aremetabolizable and support biological activity. See for example, Menaker,The Biologic Basis of Dental Caries, Chapter 16, Gibbon and Hoote, Ann.Rev. of Microbiology, 29: 19-44; and Hayes, J. Dent. Res., 2: 2-5.

The coating that remains on the hard and soft surfaces of the oralcavity after applying the preparations of the present invention is inertand substantive to the surfaces in the oral cavity. As long as this filmremains on these surfaces it:

1. disrupts the subsequent formation of "plaque-like" films on the gums,

2. imparts a smooth feeling,

3. prolongs the pleasant perception of the flavorants used in thepreparation. This prolonged flavor perception is particularly novel andunexpected and is a critical contributing factor in the high complianceprofile of the preparation of the present invention, and

4. treats the condition in the mouth with microbially active stannousfluoride.

High compliance potential is a critical element of the preparations ofthe present invention. That is, the pleasant mouth feel and low foamingproperties of these preparations and the prolonged pleasant taste andmouth feel that remains after using the preparations of the presentinvention encourages their regular use. There is a "it's working"perception of the preparations of the invention without negativemedicinal connotations which tend to reduce usage and lower compliancepotential.

Additional adjuvants can be included in the preparations of the presentinvention including:

a. Anhydrous carbohydrate sweeteners such as sorbitol and Lycasin, andhydrogenated glucose syrup, in concentrations ranging between about 1and about 15% by weight.

b. Artificial sweeteners such as acid saccharin in concentrations frombetween about 0.05 and about 3.0% by weight.

c. Anhydrous humectants such as glycerine and propylene glycol andmixtures thereof at concentrations from between about 5 and about 50% byweight.

d. flavors such as IFF vanillin 101, spearmint 082 in concentrationsfrom between about 0.1 and about 2% by weight,

e. anhydrous viscosofiers solids such as hydroxypropylcellulose,methylcellulose and carboxymethylcellulose, and

f. miscellaneous additives such as triacetin, 1-3 butylene glycol,benzyl benzoate, A-46 hydrocarbon propellant, isopentane propellant,isobutane propellant in concentrations such as set out in Table I below.

The present invention will be further illustrated with reference to thefollowing examples which aid in the understanding of the presentinvention, but which are not to be construed as limitations thereof. Allpercentages reported herein, unless otherwise specified, are percent byweight. All temperatures are expressed in degrees Celsius.

EXAMPLE 1

A spray containing one of the liquid preparations of the presentinvention was prepared containing the following substances at the % byweight indicated in parenthesis:

Sorbitol (7.5), glycerin (25) propylene glycol (23.2), absolute ethanol(40), flavor (1), saccharin (0.4), Pluronic L-64 (1.5), silicone 200(0.04), Lycasin 85% (1), and 40 mesh stannous fluoride (0.4).

This spray preparation was prepared as follows: a glass beakercontaining sorbitol, glycerin and Lycasin was magnetically stirred andheated under nitrogen to 120° C.±10°. Stannous fluoride was added withstirring until no solids remained. In a small beaker at 120° C.,Pluronic L-64 was added and stirred while Silicone 200 was added toeffect a hot-melt emulsion. This emulsion was added over one minute tothe solution of stannous fluoride with rapid stirring. Another beakerwas stirred at ambient temperature while anhydrous ethanol, propyleneglycol, saccharin and flavor was added with stirring. The stannousfluoride was added slowly with stirring and shortly after the additionwas complete, the solution became clear. The contents were thenmaintained under nitrogen.

The stannous fluoride solution was packaged in various dispensersranging from pumps to aerosols and was suitable for use in treatingconditions ranging from gingivitis, caries, Candida infections, tosensitive teeth as well as for cleaning and treating various prosthesisfor the control of Candida contamination.

Additional Examples 2-15, of liquid preparations of the invention areillustrated in Table I below.

                                      TABLE I                                     __________________________________________________________________________    EXAMPLES OF LIQUID COMPOSITIONS                                               __________________________________________________________________________                                        ABSOLUTE                                                                      ETHANOL                                   EXAMPLE                                                                              SURFACTANT                                                                             %  COATING SUBSTANCE                                                                           %  %                                         __________________________________________________________________________    2      Pluronic F127                                                                          0.2                                                                              Dow Corning 200 cs 350                                                                      0.02                                                                             38.18                                     3      Pluronic L64                                                                           0.5                                                                              Dow Corning 200 cs 350                                                                      0.05                                                                             37.85                                     4      Pluronic L64                                                                           1.0                                                                              Dow Corning 200 cs 350                                                                      0.1                                                                              37.10                                     5      Pluronic L64                                                                           2.0                                                                              Dow Corning 200 cs 350                                                                      0.2                                                                              35.4                                      6      Pluronic L64                                                                           4.0                                                                              Dow Corning 200 cs 350                                                                      0.4                                                                              33.8                                      7      Pluronic L64                                                                           2.0                                                                              Dow Corning 200 cs 100                                                                      0.2                                                                              36.0                                      8      Pluronic L64                                                                           2.0                                                                              Dow Corning 200 cs 1000                                                                     0.2                                                                              36.0                                      9      Pluronic L64                                                                           2.0                                                                              Dow Corning 360 cs 12,500                                                                   0.2                                                                              36.0                                      10     Pluronic L64                                                                           1.0                                                                              Dow Corning 1,500                                                                           0.1                                                                              48.0                                      11     PEG 400  2.0                                                                              Dow Corning 360 cs 350                                                                      0.1                                                                              55.7                                      12     T-MAZ-20 2.0                                                                              Dow Corning 200 cs 350                                                                      0.2                                                                              51.2                                      13     Pluronic L64                                                                           0.5                                                                              Dow Corning 360 cs 100                                                                      0.1                                                                              --                                               Pluronic L81                                                                           0.5                                                                              Dow Corning 360 cs 12,500                                                                   0.1                                                 Pluronic P85                                                                           0.5                                                           14     Pluronic P85                                                                           3.0                                                                              Dow Corning 200 cs 100                                                                      0.4                                                                              41.7                                             ethoxylated linear                                                                     1.0                                                                  C18-C20 alcohols                                                       15     Pluronic P85                                                                           1.0                                                                              Dow Corning 1500                                                                            0.1                                                                              37.0                                             PEG 400  0.5                                                                  ethoxylated                                                                            1.0                                                                  sorbitan laurate                                                       __________________________________________________________________________           ANHYDROUS              ANHYDROUS                                              GLYCERIN                                                                              ANHYDROUS PROPYLENE                                                                          CARBOHYDRATE                                    EXAMPLE                                                                              %       GLYCOL %       SWEETENER  %                                    __________________________________________________________________________    2      25      25             Sorbitol/Lycasin                                                                         7.5/2.5                              3      25      25             Sorbitol/Lycasin                                                                         7.5/2.5                              4      25      25             Sorbitol/Lycasin                                                                         7.5/2.5                              5      25      25             Sorbitol/Lycasin                                                                         7.5/2.5                              6        21.4  20             Sorbitol/Lycasin                                                                         10.0/5.0                             7      25      25             Sorbitol/Lycasin                                                                         10.0/5.0                             8      25      25             Sorbitol/Lycasin                                                                         10.0/5.0                             9      25      25             Sorbitol/Lycasin                                                                         10.0/5.0                             10     20      15             Sorbitol   8.0                                  11     15      10             Lycasin    5.0                                  12     --      20             --         --                                   13     20      20             Sorbitol/Lycasin                                                                         7.5/2.5                              14     30      --             Sorbitol/Lycasin                                                                         4.0/1.0                              15     20      20             --         --                                   __________________________________________________________________________           ACID                                                                   EXAMPLE                                                                              SACCHARIN                                                                              %  FLAVOR %  MISCELLANEOUS                                                                             %                                    __________________________________________________________________________    2               0.4                                                                              IDD 101                                                                              1.0                                                                              --          --                                   3               0.4                                                                              IFF 101                                                                              1.0                                                                              --          --                                   4               0.4                                                                              IFF 101                                                                              1.0                                                                              --          --                                   5               0.4                                                                              IFF 101                                                                              1.0                                                                              --          --                                   6               0.8                                                                              IFF 101                                                                              1.0                                                                              --          --                                   7               0.8                                                                              IFF 101                                                                              1.0                                                                              --          --                                   8               0.8                                                                              IFF 101                                                                              1.0                                                                              --          --                                   9               0.8                                                                              IFF 101                                                                              1.0                                                                              --          --                                   10              0.5                                                                              IFF 082                                                                              2.0                                                                              Triacetin    5                                   11              0.8                                                                              IFF 082                                                                              1.0                                                                              1-3 butylene glycol                                                                       10                                   12              1.2                                                                              IFF 101                                                                              5.0                                                                              Benzyl benzoate                                                                            5                                                                A-46-hydrocarbon                                                                          15                                                                propellant                                       13              0.4                                                                              IFF 082                                                                              1.0                                                                              Isopentane propellant                                                                     16                                   14              1.5                                                                              IFF 082                                                                              3.0                                                                              Isobutane propellant                                                                      10                                   15              2.0                                                                              IFF 101                                                                              3.0                                                                              A-46-hydrocarbon                                                                          15                                                                propellant                                       __________________________________________________________________________            EXAMPLE                                                                             SnF.sub.2 Powder %                                                                      SPECIFIC TREATMENT                                    __________________________________________________________________________            2     0.2       Oral cavity anticaries treatment                              3     0.2       Oral cavity antiplaque treatment                              4     0.4       Oral cavity for gingivitis treatment                          5     2.0       Rinse concentrate for hypersensitive teeth                    6     4.0       Rinse concentrate for denture treatment                       7     0.4       Oral cavity hypersensitive teeth treatment                    8     0.4       Oral cavity gingivitis treatment                              9     0.4       Oral cavity anticaries treatment                              10    0.4       Oral cavity antiplaque treatment                              11    0.4       Oral cavity gingivitis treatment                              12    0.4       Denture treatment spray                                             0.4                                                                     13    8.0       Rinse concentrate spray for gingivitis,                                       anticaries, plaque fighting and hypersensitive                                teeth treatment                                               14    4.0       Rinse concentrate spray for treating denture                  15    0.4       Denture treatment spray                               __________________________________________________________________________

All of the above described examples (Table I) can be modified withvarious nonionic viscosofiers to affect mouth feel, physical appearanceand the rate at which the dissolved propellent hydrocarbons effervescefrom a pressurized spray. For example, methylcellulose, hydroxypropylmethyl cellulose and hydroxypropyl cellulose, singly or in combinationsat concentrations from 0.1% to 2% are particularly efficacious.

Examples 16-22 illustrative of semi-solid preparations of the inventionare described in Table II below.

                                      TABLE II                                    __________________________________________________________________________    SEMI-SOLIDS                                                                   __________________________________________________________________________    EXAMPLE                                                                              SURFACTANT                                                                             %  COATING SUBSTANCE                                                                          %  GLYCERINE %                                                                            FLAVOR                                                                              %                           __________________________________________________________________________    16     Pluronic F127                                                                          30 Dow Corning 1500                                                                           6.3    20   IFF 101                                                                             0.3                         17     Pluronic F127                                                                          12 Dow Corning 360                                                                            2.0    15   IFF 082                                                                             0.6                                Pluronic L64                                                                           10 Medical cs 12,500                                                 Pluronic P85                                                                           10                                                            18     Pluronic F127                                                                          20 Dow Corning 200 cs 100                                                                     10     11   IFF 101                                                                             0.5                         19     Pluronic P85                                                                           25 Dow Corning 200                                                                            5  10       IFF 101                                                                             0.2                                Pluronic L64                                                                           25 cs, 65,000               IFF 082                                                                             0.1                         20     Pluronic P85                                                                           15 Dow Corning 1500                                                                           10 5        IFF 101                                                                             0.4                                ethoxylated                                                                             5                          IFF 082                                                                             0.1                                sorbitan laurate                                                       21     Pluronic F127                                                                          20 Dow Corning 200                                                                            .5 11.5     IFF 101                                                                             0.2                                polyethylene                                                                            4 cs. 350                                                           glycol 400                                                             22     Pluronic F127                                                                          20 Dow Corning 200                                                                            1.1                                                                              15.0     IFF 082                                                                             0.5                                polyethylene                                                                           10 cs. 10,000                                                        glycol 400                                                                    T-MAZ-20                                                               __________________________________________________________________________                           ABSOLUTE                                                                             ANHYDROUS     ACID                                                     ETHANOL                                                                              CARBOHYDRATE  SACCHARIN                         EXAMPLE                                                                              SOLIDS   %  %   %      SWEETENER  %  %                                 __________________________________________________________________________    16     hydroxypropyl                                                                          2.6                                                                              --  20     Sorbitol   15 .4                                       cellulose              Lycasin    5                                    17     hydroxypropyl                                                                          3  10  14.6   Sorbitol   10 .4                                       cellulose              Lycasin    10                                          methyl cellulose                                                                       2                                                             18     hydroxypropyl                                                                          3  --  10.0   Sorbitol   20 .2                                       cellulose              Lycasin    20                                          carboxymethyl                                                                          5                                                                    cellulose                                                              19     --       -- 10  10     Lycasin    13 .4                                20     carboxymethyl                                                                          10  5  12     Sorbitol   30 --                                       cellulose              Lycasin    5                                           hydroxypropyl                                                                          2.3                                                                  cellulose                                                              21     hydroxypropyl                                                                          3      20     Sorbitol   10 .4                                       methyl cellulose       Lycasin    10                                   22     hydroxypropyl                                                                          10 --  --     Sorbitol   33 --                                       methyl cellulose       (fine powder)                                          (fines)                                                                __________________________________________________________________________                       SnF.sub.2 POWDER                                                                       FORM OF                                                       EXAMPLE                                                                              %        PREPARATION                                                                            SPECIFIC TREATMENT                       __________________________________________________________________________                16     0.4      cream gel                                                                              denture treatment                                    17     0.4      gel      hypersensitive teeth treatment                       18     0.3      paste    anticaries and antigingivitis                                                 treatment                                            19     1.3      cream    denture treatment, to be                                                      used with regular toothpaste                         20     0.2      paste    hypersensitive teeth treatment                       21     0.4      gel      denture wearers, oral cavity                                                  anti-thrush treatment                                22     0.4      paste    AIDS patient, oral cavity                                                     treatment; and stomatitis                                                     treatment                                __________________________________________________________________________

The basic method of manufacturing the preparations of the presentinvention has been described in Example 1. Generally, SnF₂ issufficiently soluble in the polyhydric adjuvants used in thepreparations of the present invention such as glycerine, propyleneglycol and sorbitol to allow formulating the concentration of Sn₂desired. The requisite SnF₂ powder is dissolved in heated mixtures ofthese polyhydric adjuvants present in the preparations of the inventionsuch as described in Table I and II above.

A melt-emulsion of the otherwise incompatible components of thepreparations of the present invention, including the surfactant, coatingsubstance and flavor oil is formed as described in Example 1, and thisemulsion is blended with the polyhydric/SnF₂ solution.

When viscosofiers are required, they are preferably suspended in acomponent such as glycerine and this suspension is then added to theremainder of the preparation of the invention with vigorous agitation.

To assure SnF₂ stability during manufacturing of the preparations of thepresent invention, water and air are excluded during the variousprocessing steps.

Specifically, those components that typically contain traces of water,i.e., the polyhydric components can be placed in a jacketed, vacuumpressure vessel and heated until the water has been distilled off. Thevessel can then be blanketed with an inert gas such as nitrogen prior tothe introduction of SnF₂.

Subsequent mixing and packaging steps are carried out under similarwater and oxygen restricted conditions. Packaging materials aregenerally selected on basis of their water and oxygen barrierproperties.

Particularly preferred packages suitable for the preparations of thepresent invention include hermetically sealed dispensers such asaerosols, collapsible tubes, pressure assist pump dispensers, singledose sealed packages and barrier aerosol dispensers such as the Sepro®dispenser.

The present invention has been described in detail, including thepreferred embodiments thereof. However, it will be appreciated thatthose skilled in the art, upon consideration of the present disclosure,may make modifications and/or improvements on this invention and stillbe within the scope and spirit of this invention as set forth in thefollowing claims.

What is claimed is:
 1. The method of treating the oral cavity with anoral hygiene preparation, comprising a nonionic surfactant, a coatingsubstance insoluble in said surfactant and SnF₂ ;wherein saidpreparation: a. is non-aqueous, abrasive free, and free from substancethat interfere with the microbial activity of SnF₂, b. is characterizedas ingestible, non-foaming, and substantive to hard and soft tissue inthe oral cavity, c. has a pH from between about 3.4 and about 6.5, andd. is antimicrobially active towards s. mutans, said method comprisingthe steps of periodically introducing said preparation into the oralcavity in one of several forms selected from the group consisting ofsprays, rinses, pastes, gels and creams and retaining said preparationtherein for a period of time sufficient to treat or prevent caries,plaque and/or gingivitis therein; said preparation being convenientlystored in and dispensed from a container that is free from water andoxygen over the useful life of the preparation.
 2. A method of treatingthe oral cavity for caries with a liquid, oral hygiene preparation,comprising a nonionic surfactant, a coating substance insoluble in saidsurfactant and SnF₂ ;wherein said preparation: a. is nonaqueous,abrasive free, and free from substances that interfere with themicrobial activity of SnF₂, b. is characterized as ingestible,non-foaming, and substantive to hard and soft tissue in the oral cavity,c. has a pH from between about 3.4 and about 6.5, and d. isantimicrobially active towards S. mutans, and wherein said preparationis periodically introduced into the oral cavity as a spray dispensedfrom a hermetically sealed dispenser.
 3. A method of treating the oralcavity to reduce plaque buildup and control gingivitis with a liquidoral hygiene preparation, comprising a nonionic surfactant, a coatingsubstance insoluble in said surfactant and SnF₂ ;wherein saidpreparation: a. is nonaqueous, abrasive free, and free from substancesthat interfere with the microbial activity of SnF₂, b. is characterizedas ingestible, non-foaming, and substantive to hard and soft tissue inthe oral cavity, c. has a pH from between about 3.4 and about 6.5, andd. is antimicrobially active towards S. mutans. and wherein saidpreparation is periodically introduced into the oral cavity as a spraydispensed from a hermetically sealed dispenser.
 4. A method of treatingthe oral cavity to fight caries and reduce hypersensitivity with asemi-solid, oral hygiene preparation, comprising a nonionic surfactant,a coating substance insoluble in said surfactant and SnF₂ ;wherein saidpreparation: a. is nonaqueous, abrasive free, and free from substancesthat interfere with the microbial activity of SnF₂, b. is characterizedas ingestible, non-foaming, and substantive to hard and soft tissue inthe oral cavity, c. has a pH from between about 3.4 and about 6.5, andd. is antimicrobially active towards S. mutans, and wherein saidpreparation is periodically introduced into the oral cavity as a paste,dispensed from a collapsible tube.
 5. A method of treating the oralcavity to reduce plaque buildup and control gingivitis with a liquidconcentrate, oral hygiene preparation, comprising a nonionic surfactant,a coating substance insoluble in said surfactant and SnF₂ ;wherein saidpreparation: a. is nonaqueous, abrasive free, and free from substancesthat interfere with the microbial activity of SnF₂, b. is characterizedas ingestible, non-foaming, and substantive to hard and soft tissue inthe oral cavity, c. has a pH from between about 3.4 and about 6.5, andd. is antimicrobially active towards S. mutans. and wherein saidpreparation is periodically introduced into the oral cavity as a rinseor pre-rinse concentrate that is diluted with water after beingdispensed from a hermetically sealed dispenser.
 6. A method of treatingthe oral cavity to control S. mutans activity with semi-solid, oralhygiene preparation, comprising a nonionic surfactant, a coatingsubstance insoluble in said surfactant and SnF₂ ;wherein saidpreparation: a. is nonaqueous, abrasive free, and free from substancesthat interfere with the microbial activity of SnF₂, b. is characterizedas ingestible, non-foaming, and substantive to hard and soft tissue inthe oral cavity, c. has a pH from between about 3.4 and about 6.5, andd. is antimicrobially active towards S. mutans. and wherein saidpreparation is periodically introduced into the oral cavity as a gel,dispensed from a collapsible tube.
 7. A method of treating the oralcavity to control S. mutans activity with semi-solid, oral hygienepreparation, comprising a nonionic surfactant, a coating substanceinsoluble in said surfactant and SnF₂ ;wherein said preparation: a. isnonaqueous, abrasive free, and free from substances that interfere withthe microbial activity of SnF₂, b. is characterized as ingestible,non-foaming, and substantive to hard and soft tissue in the oral cavity,c. has a pH from between about 3.4 and about 6.5, and d. isantimicrobially active towards S. mutans, and wherein said preparationis periodically introduced into the oral cavity as a cream, dispensedfrom a collapsible tube.
 8. A method of treating prosthesis, to controlplaque buildup and candida species contamination with a sprayoral-hygiene preparation, comprising a nonionic surfactant, and SnF₂;wherein said preparation: a. is nonaqueous, abrasive free, and freefrom substances that interfere with the microbial activity of SnF₂, b.is characterized as ingestible, non-foaming, and substantive to hard andsoft tissue in the oral cavity, c. has a pH from between about 3.4 andabout 6.5, and d. is antimicrobially active towards S. mutans, andwherein said preparation is periodically sprayed onto the prosthesis,from an aerosol spray.
 9. A method of treating prosthesis, to controlplaque buildup and candida species contamination with a rinseconcentrate oral-hygiene preparation, comprising a nonionic surfactant,a coating substance insoluble in said surfactant and SnF₂ ;wherein saidpreparation: a. is nonaqueous, abrasive free, and free from substancesthat interfere with the microbial activity of SnF₂, b. is characterizedas ingestible, non-foaming, and substantive to hard and soft tissue inthe oral cavity, c. has a pH from between about 3.4 and about 6.5, andd. is antimicrobially active towards S. mutans, and wherein saidpreparation is periodically diluted and the prosthesis to be treated aresoaked in said rinse.